Therapeutic indications
1. The prophylaxis and treatment of angina pectoris.
2. Prophylaxis and treatment of supraventricular paroxysmal tachycardia; atrial
fibrillation and premature supraventricular contractions; atrial fibrillation and flutter
and supraventricular paroxysmal tachycardia of the reciprocating type, associated
with the Wolff-Parkinson-White Syndrome.
3. Treatment either alone or in conjunction with other anti-hypertensive therapy of
mild to moderate hypertension (including renal hypertension).

4.2

Posology and method of administration
Angina:
Adults:
120 mg t.d.s. is recommended. 80 mg t.d.s. can be completely
satisfactory in some patients with angina of effort. Less than 120 mg t.d.s. is not
likely to be effective in angina at rest and variant angina.

Children:

Not applicable.

Elderly:

As for adults, unless liver or renal function is impaired.

Supraventricular paroxysmal tachycardia:
Adults:

40-120 t.d.s. according to the severity of the condition.

Children:

Up to 2 years: 20 mg 2-3 t.d.s.

2 years and above: 40-120 mg 2-3 t.d.s. according to age and effect.
Elderly: It is recommended to commence with lowest dose and adjust as required.
Hypertension:
Adults: The usual dose range is 80-160 mg t.d.s. The dose should be increased from
80 mg t.d.s. at weekly intervals according to response, either alone or in conjunction
with other antihypertensive therapy. A further reduction in blood pressure may be
obtained by combining VERAMIL with other antihypertensive agents, e.g. thiazide
diuretics.
Children:

Up to 10 mg per kilo bodyweight per day in divided doses,
according to severity of disease.

Elderly: It is recommended to commence with the lowest dose and adjust as required.
Route of administration: Oral

4.3

Contraindications
Sick sinus syndrome, second or third degree atrioventricular block, cardiogenic
shock, acute myocardial infarction complicated by bradycardia, marked hypotension
or left ventricular failure, sino-atrial block, history of heart failure, bradycardia of less
than 50 beats/minute or hypotension of less than 90mmHg systolic.
Atrial flutter or fibrillation complicating Wolff-Parkinson-White syndrome.
Porphyria.
Concomitant ingestion of grapefruit juice.

4.4

Special warnings and precautions for use
Care should be exercised when beta-blockers are administered either concurrently or
closely together because the effects of beta-blockers and VERAMIL may be additive
with respect to both contraction and conduction. This is particularly important when
either drug is administered intravenously.
VERAMIL should be used with caution in patients with first-degree atrioventricular
block because impulse conduction may be affected.

Left ventricular contractility may be affected by VERAMIL because of its mode of
action; cardiac failure may therefore be precipitated or, if it already exists, may be
aggravated by VERAMIL.
It is therefore important that VERAMIL should only be administered after
appropriate
therapy for cardiac failure has been instituted, e.g. digoxin etc. Patients with impaired
liver function exhibit reduced drug metabolism and therefore careful attention should
be paid to dosage in these patients.
The disposition of verapamil in patients with renal impairment has not been fully
established and therefore careful patient monitoring is recommended. Verapamil is
not
removed during dialysis.
VERAMIL should not be used in children with arrhythmias without specialist advice;
some supraventricular arrhythmias in childhood can be accelerated by verapamil with
dangerous consequences.
Patients starting therapy with simvastatin should be advised of the risk of myopathy
and told to report promptly unexplained muscle pain, tenderness or weakness. A CPK
level above 10x ULN in a patient with unexplained muscle symptoms indicates
myopathy. Simvastatin therapy should be discontinued if myopathy is diagnosed or
suspected. Periodic CPK determinations may be considered (see section 4.5
‘Interactions with other Medicaments and forms of Interaction’).
Patients with rare hereditary problems of galactose intolerance, Lapp lactase
deficiency or glucose/galactose malabsorbtion should not take Veramil.

4.5

Interaction with other medicinal products and other forms of interaction
VERAMIL increases the serum concentration of digoxin with increased risk AV
block and bradycardia; the awareness of the possibility of digitalis toxicity should
also be borne in mind.
Verapamil also increases the plasma concentration of imipramine and possibly other
tricyclics, ciclosporin, theophylline and drugs under CYP-450 system (e.g. buspirone,
dutasteride, eplerenone, atazanavir, ritonavir, sirolimus simvastatin).
There is an increased risk of myopathy when verapamil is given with simvastatin (see
section 4.4 ‘Special Warnings and Precautions for Use’).

Concomitant use of verapamil and intravenous dantrolene may cause hypotension,
myocardial depression and hyperkalaemia.
Grapefruit juice - an increase in verapamil serum level has been reported.
The effects of verapamil may be additive to other drugs which can produce a
hypotensive
effect. Examples of these are alcohol, aldesleukin, alprostadil, and anaesthetics with
risk of AV delay, antihypertensives, diuretics, antipsychotics, anxiolytics &
hypnotics, baclofen, isoflurane, levodopa, MAOIs, nitrates, nitroprusside and
tizanidine.
Hypotensive effect of calcium-channel blockers e.g. verapamil is antagonised with
concomitant use of NSAIDs, corticosteroids or oestrogens.
Concomitant use of beta-blockers and verapamil may cause severe hypotension and
even
heart failure and should only be given together if myocardial function is well
preserved.
Enhanced hypotensive effect has been reported when calcium channel blockers are
given
with alpha-blockers. There is also an increased risk of first-dose hypotension with
postsynaptic alpha-blockers such as prazosin.
Cimetidine may inhibit metabolism of verapamil causing increased verapamil-plasma
concentrations.
Amiodarone-induced risk of bradycardia, AV block and myocardial depression is
increased by verapamil.

There is possibly increased risk of bradycardia when calcium-channel blockers are
given with mefloquine.
Concomitant use of verapamil with disopyramide and flecainide increases risk of
myocardial depression and asystole.
Verapamil may raise the plasma concentration of quinidine resulting in extreme
hypotension.
Rifampicin increases the metabolism of verapamil thereby significantly reducing its
plasma concentration.
The effect of verapamil is also reduced by phenobarbitol, primidone and phenytoin.
Neurotoxicity may occur without increased plasma-lithium concentrations in patients
given verapamil.

4.6

Pregnancy and lactation
Verapamil is not recommended for use during pregnancy unless the benefits of the
drug outweigh the possible hazards to the foetus.

4.7

Effects on ability to drive and use machines
Depending on individual susceptibility, the patient’s ability to drive a vehicle or
operate machinery may be impaired, particularly in the initial stages of treatment, or
when changing over from another drug. Verapamil has been shown to increase the
blood levels of alcohol and slow its elimination. Therefore, the effects of alcohol may
be exaggerated.

Overdose
The classical measures for cardiovascular side effects should be instituted
immediately. Cardiac arrest should be treated by heart massage, mechanical
respiration and the necessary intensive are appropriate to the condition should be
instituted.
In the case of hypotension, dopamine, noradrenalin or dobutamine may be used
together with appropriate positioning of the patient. Likewise, in myocardial
insufficiency treatment should be either dopamine, dobutamine, cardiac glucosides or
10-20 ml of a 10% solution of calcium gluconate. Second or third degree AV block
should be treated with atropine or isoprenaline and if necessary a pace maker should
be used.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Verapamil is a Class 4 anti-arrhythmic agent which acts on supraventricular
arrhythmias through interfering with calcium conductants.

5.2

Pharmacokinetic properties
Verapamil is almost completely absorbed from the gastro-intestinal tract but is
subject to very considerable first-pass metabolism in the liver. The plasma half-life is
about 7 hours following oral administration and that of its active metabolite which is
norverapamil is about nine hours.
Verapamil acts within minutes of intravenous administration but its effects may only
last for about half-an-hour. It may require two hours to act after oral administration
with peak effect after five hours.
Verapamil is extensively bound to plasma proteins. The drug is mainly excreted by
the kidneys in the form of its metabolites, but some is also excreted in the bile and in
the faeces.

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.